The effect of acute and subsequently chronic administration of various chemical constituents of marijuana with putative psychoactive actions will be determined on acetylcholine (ACH) content, release, utilization and turnover in various regions of the rat brain. Eight major regions of the rat brain will be studied including the cerebral cortex, cerebellum, medulla oblongata, thalamus hypothalamus, striatum, hippocampus and midbrain. Content and release of ACH will be measured by gas chromatography and mass spectrometry. Release will be obtained using the push-pull cannula technique. Utiliztion of brain ACH, an indirect measure of turnover, will be measured using the choline acetyltransferase inhibitor, acetylseco hemicholinium-3. Turnover will be measured by giving labeled choline. The dose-related and time- related effects of various natural cannabinoids and synthetic derivatives will be studied on acute and chronic administration. The more important psychoactive derivatives such as delta 9-THC and DMHP will be studed extensively but cannabinol, cannabidiol, cannabigerol, cannabidiolic acid and various other minor THC constituents will be examined, especially to dissociate sedative and psychotomimetic properties. Daily and bid chronic injections for several weeks will be used to study tolerance and cross-tolerance to other psychotropic drugs like ethyl alcohol. Some selected experiments will be done in the Macaca mulatta monkey as a species phylogenetically close to man. This research will clarify the role of brain ACh in marijuana intoxication in man.